Anti-Gal alpha 1-3Gal IgM/IgG antibody levels in infants: Do they have a clinical relevance in pediatric xenotransplantation?

Background: Anti-Gal alpha1-3Gal antibodies (anti-Gal) compose a major obst acle to xenotransplantation. As it is known, there is an immunological wind ow during which infants are thought to have no xenoreactive antibodies. The refore, we were interested in investigating the occurrence of these antibod ies in newborns and infants up to 2 years of age. Methods: IgM/IgG isotypes of anti-Gal from 74 serum samples of 16 mothers, with the respective cord bloods, and 42 infants of 4 age groups (Group I: d ay 1-6 months, II: 7-12 months, III: 13-18 months, and IV: 19-24 months) we re determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA). A synthetic Ga l alpha1-3Gal disaccharide-polyacrylamide glycoconjugate was used for coati ng and monoclonal antibodies were used for the detection of heavy chain iso types. Antibody concentrations were referred to an internal standard and ex pressed as arbitrary ELISA units (U), Hemagglutination titers against rabbi t erythrocytes (E-R) were determined in addition. Results: Maternal serum samples showed a wide interindividual variability ( IgM: 87 +/- 33 U (mean +/- SD), IgG 59 +/- 39 U) whereas in cord blood no d etectable IgM was seen in presence of IgG (52 +/- 34 U). From Group I to IV there was a gradual increase of anti-Gal IgM towards an average of 70% of the adult levels whereas IgG fell to an average of similar to 20% of cord b lood levels. Hemagglutination titers followed an increasing tendency with c ord blood starting from 1:16 and reaching 1:256 in Group IV. Conclusion: The humoral immune response to the Gal alpha1-3Gal epitope (alp ha -Gal) in infancy follows the generally known development of specific ant ibodies in humans.